Trial Title:
Exogenous and Endogenous Risk Factors for Early-onset Colorectal Cancer
NCT ID:
NCT05732623
Condition:
Colorectal Cancer
Early Onset Colorectal Cancer
Diet Habit
Risk Reduction
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Early onset
Young onset
Young adult
Colon cancer
Rectal cancer
Cancer genetics
Cancer risk factors
Diet
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Behavioral
Intervention name:
Semi Quantitative Food Frequency Questionnaire (SQFFQ)
Description:
The SQFFQ quantifies the frequency of consumption of each food and drink and the
following list of variables:
- date of birth
- sex
- ethnicity
- weight (kg)
- height (m)
- BMI (kg/m2) at the time of eoCRC diagnosis and at 18 years old
- country where they live permanently
- tobacco smoking at the time of eoCRC diagnosis and at 18 years old
- sitting time
- TV-viewing time
- moderate-to-vigorous physical activity (MVPA)
- waist circumference (cm)
- home blood pressure levels (mmHg)
- fasting blood glucose (mg/dl)
- regular consumption of aspirin/NSAID and years of consumptions
- calcium and folate supplements and years of consumptions
- oral contraceptive agents and years of consumptions
- post-menopausal hormones and years of consumptions
Arm group label:
Control
Arm group label:
Early onset colorectal cancer
Summary:
An increase in early-onset colorectal cancers (eoCRC), defined as a CRC before 50 years,
is confirmed globally.
CRC pathogenesis has been associated with several risk factors (family history, germline
pathogenic variants, obesity, alcohol, physical activity, red meat, and a Western diet).
Design: an international, multicenter, retrospective case-control study of prospectively
enrolled patients; low-risk intervention study as it will perform a fecal occult blood
test Endpoint: predictive power of a semi-quantitative food frequency questionnaire
(SQFFQ) developed for eoCRC.
Cases: Patients with a recent diagnosis of eoCRC (within 2 years from enrollment).
Controls: matched by age (matching range ± 5 years) and sex. Healthy volunteers will be
mainly enrolled among workers within the participating hospital center. The enrolled
healthy volunteers will perform a fecal occult blood test.
Variables of interest: age, sex, ethnicity, BMI at the time of eoCRC diagnosis and at 18
years old, country, tobacco smoking at the time of eoCRC diagnosis and at 18 years old,
sitting time, TV-viewing time, moderate-to-vigorous physical activity (MVPA), waist
circumference (cm), home blood pressure levels (mmHg), fasting blood glucose (mg/dl),
regular consumption of aspirin/NSAID, calcium and folate supplements, oral contraceptive
agents, post-menopausal hormones and years of consumptions, if the filled questionnaire
reflects diet for the last 5-10 years before.
Cases only: date of eoCRC diagnosis, symptoms at diagnosis, eoCRC localization, eoCRC
stage, histological diagnosis, type of surgery, and date (if performed), chemotherapy and
radiotherapy (if performed), vital status and duration of follow-up, family history of
CRC and other cancers (uterus, ovary, stomach, small intestine, urinary
tract/bladder/kidney, bile ducts, brain, pancreas, skin tumors), type of germline
pathogenetic variant (if performed).
Before the case-control study, three non-consecutive 24-hour Dietary Recalls (24hDRs)
will validate the SQFFQ.
The SQFFQ will be administered to the validation study group during three non-consecutive
calls, including one non-weekday (30-minute 24-h-recall computer-aided personal
interview).
Primary Objective To measure the relative risk of specific dietary and lifestyle factors
(smoking habit, alcohol intake, physical activity) for early-onset colorectal cancer in
countries where eoCRC incidence is increasing versus stable/decreasing
Detailed description:
Background Firstly described in U.S. series, an increase in early-onset colorectal
cancers (eoCRC), defined as CRC before 50 years, is confirmed globally.
CRC pathogenesis has been associated with several endogenous and exogenous associated
risk factors, including family history of CRC, CRC-related germline pathogenic variants,
obesity, alcohol habits, physical activity, red and processed meat and a Western diet.
Two dietary patterns appear as exogenous and behavioral factors associated with either
CRC prevention or predisposition: the 'healthy' pattern (high in fruits, vegetables, and
whole grains or legumes, fish, and low-fat milk or dairy products) and the 'unhealthy' or
'Western dietary' pattern (high in red and processed meat, sugary drinks, refined grains,
desserts). Above all, the Western diet is one of the most important CRC risk factors. In
the Nurses' Health Study II, Western diet during adolescence was associated with the
development of high-risk rectal adenomas later in life. In a meta-analysis of cohort
studies, the Western dietary pattern conferred a relative risk (RR) of 1.12 for CRC,
compared with a 0.89 RR for the healthy pattern. Conversely, the Mediterranean diet
demonstrated a protective role in CRC development, confirmed in the EPIC cohort study.
Rationale Dietary, lifestyle, and anthropometric risk factors are still poorly understood
in eoCRC patients, despite its established rising incidence. To date, scant studies,
mostly case-control and only a few prospective ones, investigated the exogenous risk
factors of eoCRCs and eoCRC precursors and identified high intake of alcohol and
processed meat, sedentary lifestyle as potential eoCRC risk factors, and obesity as
ambiguous one.
Primary Objective To compare the associations of specific dietary and lifestyle factors
(smoking habit, alcohol intake, physical activity) and anthropometric factors between
eoCRC patients and healthy age- and sex-matched controls in countries with increasing
versus stable or decreasing early-onset colorectal cancer (eoCRC) incidence.
Secondary Objectives
1. To validate the semi-quantitative food frequency questionnaire (SQFFQ);
2. To evaluate the consistency of associations across cohorts in pairwise comparisons;
3. To assess whether associations differ among specific population subgroups (e.g.,
sex, ethnicity, smoking habits, BMI, physical activity, family history of CRC).
Type of study SQFFQ validation study: three non-consecutive 24-hour Dietary Recalls
(24hDRs) will validate the ad hoc designed and shared SQFFQ, as previously performed
[28-29]. The SQFFQ will be administered to the validation study group during three
non-consecutive calls, including one non-weekday (30 minutes 24-h-recall computer-aided
personal interview).
Case-control study: an international, multicentre, retrospective case-control study of
prospectively enrolled patients will be performed to evaluate the associations of
dietary, anthropometric, lifestyle factors in eoCRC patients compared to age, and sex
matched healthy controls.
This study is sub-classified as a low-risk intervention study as it will perform fecal
occult blood test as an additional procedure in the control group.
Inclusion criteria All sexes eligible Cases: eoCRC diagnosed between 18 and 49 years and
confirmed by histology (biopsy or surgical specimen in case of surgery) Controls:
negative past and present history of cancer; negative fecal occult blood test (FOBT), or
negative colonoscopy.
Exclusion criteria CRC diagnosed at ≥ 50 years Diseases that can modify the dietary
regimen (celiac disease, diabetes) Diseases that are known to predispose to eoCRC
(personal past or recent history of inflammatory bowel disease, past history of pelvic
irradiation) Unable to give written consents and to fill in the electronic questionnaire
Sample size
SQFFQ Validation study:
- 100 subjects from each country, free from overt disease and in equal numbers of each
gender.
Case-control study:
- At least 300 eoCRC patients in total;
- At least 600 healthy age- (matching range ± 5 years) and sex-matched controls
subjects in total.
Study Procedure and Study Flow-chart Starting from the signature of the informed consent
by the subject/patient (or subject/patient's legal tutor), she/he will be considered
enrolled in the study.
The PI will be the only Administrator of the online platform and the only one able to
generate the access codes (username/password) assigned to the co-investigators.
Each co-investigator will register the enrolled subjects anonymously on the online
platform (unique alphanumeric identification code - see below), obtaining a
username/password assigned to the subject for survey completion.
The unique alphanumeric identification code (Subject ID number) will be assigned
consecutively in increasing order starting from '001'. A screened subject/patient
identification list will be kept by PI.
SQFFQ validation study:
One hundred volunteers from each country, free from overt disease and in equal numbers of
each sex, will be enrolled for the semi-quantitative food frequency questionnaire (SQFFQ)
validation study. Potential volunteers will be recruited through different recruitment
strategies: mail drops, recruitment lists, and databases, primary care facilities as well
as networks for young people and/or among people who work in the same hospital of the
research team, regularly followed by preventive medicine.
An ad hoc-designed and shared online SQFFQ will be available to report the usual
frequency of consumption of a detailed list of foods and beverages. Information collected
concern types, amount and frequency of consumption of food and drinks, types of
seasoning, and methods of cooking. The computer-administered instrument will allow the
respondent to select the food consumed and the appropriate portion size from photographs
on a screen reducing the burden of coding.
All volunteers will receive detailed oral and written information by members of the study
team (following local practices).
Three non-consecutive 24-hour Dietary Recalls (24hDRs), including one non-weekday (30
minutes 24-h-recall computer-aided personal interview), will validate the SQFFQ [28-29].
Case-control study:
An international, multicentre, retrospective case-control study of prospectively enrolled
patients will be performed to evaluate the associations of dietary, anthropometric,
lifestyle factors in eoCRC patients compared to age, and sex matched healthy controls.
This study is sub-classified as a low-risk intervention study as it will perform fecal
occult blood test as an additional procedure in the control group.
The study will recruit:
- at least 300 patients in total (100 at IRCCS San Raffaele Scientific Institute) with
a recent diagnosis of eoCRC (diagnosis made within 2 years prior to enrollment),
aged 18-49 years, will be prospectively recruited. eoCRC patients will be primarily
enrolled as referred by the participant unit. Each participant unit shall identify
eoCRC patients through recruitment lists and databases, primary care facilities, as
well as networks for young people. Retrospective data (dietary and lifestyle
factors) related to the 2 years prior to eoCRC diagnosis will be collected through
an online platform.
- at least 600 Healthy controls (HCs) totally (200 at IRCCS San Raffaele Scientific
Institute), matched by age (matching range ± 5 years) and sex with eoCRCs will be
prospectively enrolled. Healthy volunteers will be mainly enrolled among workers
within the participating hospital center, followed regularly by preventive medicine.
This enrollment will be carried out by e-mail invitation disseminated through the
hospital's official mailing list. The enrolled healthy volunteers will perform fecal
occult blood test as an additional procedure and will be enrolled if this test is
negative. Retrospective data (dietary and lifestyle factors) related to the 2 years
prior to recruitment will be collected through an online platform.
The online platform will be divided into two separate sections: (i) one completed by
cases / controls, concerning the semi-quantitative food frequency questionnaire (SQFFQ),
lifestyle habits and anthropometric data; (ii) one completed by doctors, concerning
clinical data.
The semi-quantitative food frequency approach will ask to report their usual frequency of
consumption of each food and drink, referred to the two years before eoCRC onset,
following detailed oral and written instructions from the members of the study team.
Information collected will concern types, amount and frequency of consumption of food and
drinks, types of seasoning, and methods of cooking. A computer-administered instrument
will allow the respondent to select the food consumed and the appropriate portion size
from photographs on a screen reducing the burden of coding.
All cases and healthy controls will also provide a set of covariates as part of the
online platform: date of birth, sex, ethnicity, weight (kg)/height (m)/BMI (kg/m2) at the
time of eoCRC diagnosis and at 18 years old, country where the patient/healthy control
lives permanently, tobacco smoking at the time of eoCRC diagnosis and at 18 years old,
sitting time, TV-viewing time, moderate-to-vigorous physical activity (MVPA), waist
circumference (cm), home blood pressure levels (mmHg), fasting blood glucose (mg/dl),
regular consumption of aspirin/NSAID, calcium and folate supplements, oral contraceptive
agents, post-menopausal hormones and years of consumptions, if the filled questionnaire
reflects diet for the last 5-10 years before.
Other clinical data will be collected by doctors as part of the online platform: date of
eoCRC diagnosis, symptoms at diagnosis, eoCRC localization, eoCRC stage, histological
diagnosis, type of surgery and date (if performed), chemoterapy and radiotherapy (if
performed), vital status and duration of follow-up, family history of CRC and other
cancers (uterus, ovary, stomach, small intestine, urinary tract/bladder/kidney, bile
ducts, brain, pancreas, skin tumors), type of germline pathogenetic variant (if
performed).
4.6 Responsibilities of the Investigator(s) The Investigator(s) undertake(s) to perform
the study in accordance with this Protocol, Good Clinical Practice and the applicable
regulatory requirements.
The Investigator is required to ensure compliance with the investigational schedule, and
procedures required by the protocol.
The Investigator agrees to provide all information requested in the Case Report Form
-CRF- in an accurate and legible manner.
ETHICAL CONSIDERATIONS Ethical conduct of the study The study will be performed according
the ethical principles laid down in the latest accepted version of the Declaration of
Helsinki.
Patient information and informed consent Each subject/patient will be informed about the
modalities of the clinical study in accordance with the enclosed patient information. The
subject/patient is to be informed both in writing and verbally by the investigating
physician. The subject/patient must be given opportunity to decide whether or not to
participate in this study and to ask questions concerning this. It must also be made
clear to the subject/patient that he/she can withdraw from the study at any time without
giving reasons and that he/she will not be in any way disadvantaged by this. The points
mentioned in the information sheet must be communicated to the patient in language he/she
understands. The informing physician and the patient must each personally date and sign
an informed consent form with a declaration on data privacy. Any informed consent will be
part of the investigator's file and retained with it. The subject/patient will retain a
copy of the patient information.
Data management The personal data will be recorded in the electronic CRF designed for
this study. All CRF will be checked for completeness, plausibility, and compliance with
the ICH guidelines and the institutional Standard Operating Procedures (SOPs).
The personal data will be identified with a code (see section 6.7) not allowing directly
trace the identity of the patients/individuals, except in case of need. In all phases of
collection and processing of personal data, suitable measures will be adopted to
guarantee their protection from the risks of unauthorized access, theft or loss, also
through the use of encryption techniques, identification codes or other solutions that
allow identify the interested parties only in case of need and to those who are expressly
authorized to access them, in order to minimize the risks of accidental knowledge and
unauthorized or abusive access to data. The genetic and clinical data of the interested
parties are, however, treated separately from other "common" personal data (name,
surname, etc.), which allow the interested parties to be directly identified.
The collection, management and analysis of data will take place in a way that guarantees
the confidentiality of the subject's identity and will follow the General Data Protection
Regulations (GDPR).
With regard to the possible transfer of data to third countries, the processing will take
place according to one of the methods permitted by current law, such as the consent given
by the patients/individuals, the adoption of Standard Clauses approved by the European
Commission, the selection of subjects adhering to international programs for the free
circulation of data (eg EU-USA Privacy Shield) or operating in countries considered safe
by the European Commission.
All analyses will be performed within respective limitations of each ethics committee
approval and in accordance with good clinical practice and the Declaration of Helsinki.
Sample size
SQFFQ Validation study:
100 subjects from each country, free from overt disease and in equal numbers of each
gender.
Case-control study:
Power analysis for odds ratios calculation The odds ratios of eoCRC for different
exposition factors will be calculated.
For this purpose, a power analysis is performed, based on the following parameters:
- Significance level (alpha, 1 type error probability) = 0.05 (two tails test)
- Power of the analysis = 80%
- Number of controls per case = 2
- Minimum Odds Ratio to detect = 2
- Proportion of exposed in the general population The proportion of exposed
individuals in the general population depends on the considered exposition factors
(such as a specific diet habit, alcohol consumption, etc.): for this reason, the
sample size was calculated for different exposition proportions, varying from 5% to
95%.
Statistical analysis
SQFFQ validation Study:
The validity of the SQFFQ will be computed by calculating the Spearman correlation
coefficients between individual food groups intakes from SQFFQ and the average of three
24hDR food groups intakes as the reference method.
The percentage of the agreement as the proportions of individuals who were classified
correctly into the same or adjacent quintile for validity analyses will be calculated.
Case-control Study:
In the case-control study, an association between eoCRC and dietary habits (or other
exposition factors such as alcohol consumption, smoking habits, etc.) will be estimated
using logistic regression and odds ratio calculation. Multivariate logistic regression
models will be used to examine to what extent eoCRC development can be 'explained' by
variations in eating habits. The stratified analysis will also be performed by
considering only a specific gender and/or other grouping variables of interest such as
age, age at diagnosis. The effects of potential confounders other than matching criteria
(e.g., smoking, physical activity, etc.) will also be estimated and taken into account.
All analyses are based on a conservative estimate of eoCRC cancer cases, with at least 2
controls per case.
Criteria for eligibility:
Study pop:
at least 300 patients in total (100 at IRCCS San Raffaele Scientific Institute) with a
recent diagnosis of eoCRC (diagnosis made within 2 years prior to enrollment), aged 18-49
years, will be prospectively recruited at least 600 Healthy controls (HCs) totally (200
at IRCCS San Raffaele Scientific Institute), matched by age (matching range ± 5 years)
and sex with eoCRCs will be prospectively enrolled. Healthy volunteers will be mainly
enrolled among workers within the participating hospital center, followed regularly by
preventive medicine. This enrollment will be carried out by e-mail invitation
disseminated through the hospital's official mailing list
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
- All sexes eligible
- (for Cases) eoCRC diagnosed between 18 and 49 years and confirmed by histology
(biopsy or surgical specimen in case of surgery)
- (for Controls) negative past and present history of cancer; negative fecal occult
blood test (FOBT), or negative colonoscopy.
Exclusion Criteria:
- CRC diagnosed at ≥ 50 years
- Diseases that can modify the dietary regimen (celiac disease, diabetes)
- Diseases that are known to predispose to eoCRC (personal past or recent history of
inflammatory bowel disease, past history of pelvic irradiation)
- Unable to give written consents and to fill in the electronic questionnaire
Gender:
All
Minimum age:
18 Years
Maximum age:
49 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Department of Medicine-Gastroenterology, Denver Veterans Affairs Medical Center, University of Colorado Hospital
Address:
City:
Denver
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Swati Patel
Email:
Swati.Patel@cuanschutz.edu
Facility:
Name:
Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine University of Chicago Medicine
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sonia Kupfer
Email:
skupfer@medicine.bsd.uchicago.edu
Facility:
Name:
Department of Gastrointestinal Surgery, Helsinki University Hospital
Address:
City:
Helsinki
Country:
Finland
Status:
Recruiting
Contact:
Last name:
Toni T Seppala
Email:
tseppala@me.com
Facility:
Name:
Department of General, Visceral and Transplant Surgery, Hospital of the University of Munich (LMU)
Address:
City:
Munich
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Florian Kuhn, MD
Email:
Florian.Kuehn@med.uni-muenchen.de
Facility:
Name:
Gabriela Moslein
Address:
City:
Wuppertal
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Gabriela Moslein, MD
Email:
gmoeslein@outlook.de
Facility:
Name:
Prof Giulia Martina Cavestro, MD PhD
Address:
City:
Milan
Zip:
20132
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Giulia Martina Cavestro, MD, PhD
Phone:
0226435508
Phone ext:
+39
Email:
cavestro.giuliamartina@hsr.it
Investigator:
Last name:
Marta Puzzono, MD
Email:
Sub-Investigator
Investigator:
Last name:
Alessandro Mannucci, MD
Email:
Sub-Investigator
Facility:
Name:
Division of Cancer Medicine, Oslo University Hospital (OUS), Institute for Cancer Genetics and Informatics Norwegian Radium Hospital
Address:
City:
Oslo
Country:
Norway
Status:
Recruiting
Contact:
Last name:
Mev Dominguez Valentin
Email:
mev.dominguez.valentin@rr-research.no
Facility:
Name:
Department of Gastroenterology, Hospital Clínic de Barcelona, University of Barcelona
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Francesc Balaguer Prunès
Email:
FPRUNES@clinic.cat
Start date:
December 5, 2022
Completion date:
January 2035
Lead sponsor:
Agency:
San Raffaele University
Agency class:
Other
Collaborator:
Agency:
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Agency class:
Other
Collaborator:
Agency:
Ospedale Civile Guglielmo da Saliceto, Piacenza, Italy
Agency class:
Other
Collaborator:
Agency:
Centro di Riferimento Oncologico di Aviano, Aviano, Italy
Agency class:
Other
Collaborator:
Agency:
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy
Agency class:
Other
Collaborator:
Agency:
Gastroenterology Unit, University Hospital of Padova, Padova, Italy
Agency class:
Other
Collaborator:
Agency:
Clinical Gastroenterology Unit, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy
Agency class:
Other
Collaborator:
Agency:
IRCCS Arcispedale S. Maria Nuova - Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy
Agency class:
Other
Collaborator:
Agency:
Azienda Ospedaliera San Gerardo di Monza, Monza, Italy
Agency class:
Other
Collaborator:
Agency:
Azienda ULSS5 Polesana, Rovigo, Italy
Agency class:
Other
Collaborator:
Agency:
Istituto Tumori Regina Elena - IRCCS IFO, Roma, Italy
Agency class:
Other
Collaborator:
Agency:
University Hospital of Padova, Padova, Italy
Agency class:
Other
Collaborator:
Agency:
IRCCS De Bellis, Castellana Grotte, Italy
Agency class:
Other
Collaborator:
Agency:
University Hospital HELIOS Klinikum Wuppertal, Center for Hereditary Tumors, University of Witten-Herdecke, Wuppertal, Germany
Agency class:
Other
Collaborator:
Agency:
Hospital of the University of Munich (LMU), Campus Großhadern, Munich, Germany
Agency class:
Other
Collaborator:
Agency:
Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
Agency class:
Other
Collaborator:
Agency:
Helsinki University Hospital, Helsinki, Finland
Agency class:
Other
Collaborator:
Agency:
Oslo University Hospital (OUS), Institute for Cancer Genetics and Informatics Norwegian Radium Hospital, Oslo, Norway
Agency class:
Other
Collaborator:
Agency:
Department of Medicine University of Chicago Medicine, Illinois, USA
Agency class:
Other
Collaborator:
Agency:
University of Colorado Hospital, CO, USA
Agency class:
Other
Collaborator:
Agency:
University of Michigan Ann Arbor, Michigan, USA
Agency class:
Other
Collaborator:
Agency:
Columbia University Irving Medical Center, New York, NY
Agency class:
Other
Collaborator:
Agency:
The James Comprehensive Cancer Center, Columbus, OH, USA
Agency class:
Other
Collaborator:
Agency:
Ohio State University
Agency class:
Other
Collaborator:
Agency:
Cleveland Clinic Main Campus, Cleveland, OH, USA
Agency class:
Other
Collaborator:
Agency:
Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
Agency class:
Other
Source:
San Raffaele University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05732623
http://www.fondazione-menarini.it/Home/Eventi/Early-onset-Colorectal-Cancer/813/Presentazione
https://www.youtube.com/watch?v=JlpciBBFg5k
